Intermittent intravenous cyclophosphamide therapy for lupus nephritis Thomas J. A. Lehman, MD, David D. Sherry, MD, Linda Wagner-Weiner, MD, Deborah K. McCurdy, MD, Helen M. Emery, MD, Daniel B. Magilavy, MD, and Andrea Kovalesky, RN From the Division of Pediatric Rheumatology, the Hospital for Special Surgery, and the Department of Pediatrics, Cornell University Medical Center, New York; the Division of Pediatric Rheumatology, the University of Washington School of Medicine, Seattle; the Department of Pediatrics, University of Chicago and La Rabida Children's Hospital, Chicago; and the Division of Rheumatology, Childrens Hospital of Los Angeles, and the Department of Pediatrics, University of Southern California at Los Angeles We carried out a preliminary study to determine whether intermittent intrave- nous cyclophosphamide therapy could be safely and effectively used in the treatment of childhood lupus nephritis. Sixteen children (4 to 18 years of age) with lupus nephritis were treated with cyclophosphamide monthly for 6 months and then every 3 months. Eight children were treated because of corticoste- roid-unresponsive active lupus nephritis, with a fall in their creatinine clear- ance to <100 ml/min/1.75 m 2, and eight children were treated because of corticosteroid-dependent nephrotic syndrome or active lupus nephritis with unacceptable corticosteroid-induced side effects. Cyclophosphamide treat- ment was associated with significant improvement at 1 year in mean levels of hemoglobin (11.3 • 0.5 to 13.1 +_ 0.3 gm/dl), C3 (52 • 5.9 to 108 +_ 13.7 mg/dl), and C4 (7.6 • 0.9 to 15.9 +_ 2.2 mg/dl) (all p <0.005), despite a significant reduction in mean prednisone dosage (31 • 5 to 14 • 2 mg/day; p <0.005). There was a decrease in 24-hour urine protein excretion from 3121 • 913 to 1016 • 364 mg/24 hours (p <0.05). For children whose initial creatinine clear- ance was less than 100 ml/min/1.75 m 2, creatinine clearance also improved significantly (57.5 • 11 to 121 _+ 24.5 ml/min/1.75 m2; p <0.05). The long-term safety of intravenous cyclophosphamide therapy and its long-term efficacy in comparison with prednisone alone remain to be established. In the interim, intravenous cyclophosphamide therapy should be reserved for children with severe, unacceptable corticosteroid side effects or with corticosteroid-resis- tant and potentially life-threatening disease. (J PEDIATR i989;114:1055-60) Although the overall prognosis for children with systemic lupus erythematosus continues to improve, the presence of lupus nephritis remains a major predictor of morbidity and mortality rates for childhood SLE. 1 Childhood SLE com- Submitted for publication July 20, 1988; accepted Dec. 1, 1988. Reprint requests: Thomas J. A. Lehman, MD, Chief, Division of Pediatric Rheumatology, The Hospital for Special Surgery, 535 E. 70th St., New York, NY 10021. plicated by diffuse proliferative lupus nephritis may improve with long-term corticosteroid therapy, but pro- gression to chronic renal failure remains commonplace. 2, 3 Complications of prolonged cortlcosteroid therapy include growth retardation, increased risk of infection, osteoporo- sis, avascular necrosis, and undesirable cosmetic changes. Controlled, prospective studies of intravenous cyclophos- phamide therapy for lupus nephritis in adults have demon- strated it to be well tolerated and associated with improved long-term outcome. 4-6 1055